Peripheral neurotrophin levels during controlled crack/cocaine abstinence: a systematic review and meta-analysis.

Cocaine/crack abstinence periods have higher risk of relapse. Abstinence as initial part of the recovery process is affected by learning and memory changes that could preserve the addictive cycle. To further understand how the interruption of cocaine/crack consumption affects neurotrophin level we performed the present systematic review and meta-analysis following the PRISMA statement (number CRD42019121643). The search formula was conducted in PubMed, Web of Science, Embase, ScienceDirect, and Google Scholar databases. The inclusion criterion was cocaine use disorder in 18 to 60-year-old people, measuring at least one neurotrophin in blood before and after a controlled abstinence period. Studies without pre-post design were excluded. Five investigations had nine different reports, four of them were subjected to a meta-analysis (n = 146). GRADE risk of bias method was followed. Individual studies reported increased peripheral brain derived neurotrophic factor (BDNF) after abstinence, evidence pooled by Hedge's g showed no significant change in BDNF after abstinence. Relevant heterogeneity in the length of the abstinence period (12-32 days), last cocaine/crack consumption monitoring and blood processing were detected that could help to explain non-significant results. Further improved methods are suggested, and a potential BDNF augmentation hypothesis is proposed that, if true, would help to understand initial abstinence as a re-adaptation period influenced by neurotrophins such as the BDNF.

Cognitive functions of subjects with cocaine and crack dependency disorder during early abstinence. / Funcionamiento cognitivo en sujetos con trastorno de dependencia a cocaina y crack durante la abstinencia temprana.

INTRODUCTION: Cognitive effects caused by cocaine and crack consumption, especially deficits in executive functions may increase the likelihood of drug-seeking behaviour and interfere with the ability of users to assimilate and participate in rehabilitation programs. AIM: To determine in early abstinence the state of executive functions, the impulsiveness and craving in cocaine and crack consumers. SUBJECTS AND METHODS: This cross-sectional study functions, with a sample of 60 male aged between 31.38 ± 7.26 years old, distributed in three groups: inhaled cocaine users (CDP-I; n = 15), with 23.13 ± 7.2 age of onset of consumption; crack cocaine users (CDP-C; n = 26), with 20.81 ± 4.21 age of onset of consumption, and a control groups of no-addiction individuals (n = 19). Sociodemographic, clinical and cognitive assessments were applied. RESULTS: The data showed that significant differences in socioeconomic level score and impulsiveness. Consumer groups have with lower scores with respect the control group. CDP-C group showed poor performances compared to the CDP-I and control groups, in the Berg Test, Tower of London, numbers in the direct order and subtraction. CDP-I group showed less score in planning compare with the other two groups. CONCLUSIONS: In early abstinence crack users manifest a greater number of deficits, mainly in working memory, planning and cognitive flexibility.

TITLE: Funcionamiento cognitivo en sujetos con trastorno de dependencia a cocaina y crack durante la abstinencia temprana.Introduccion. Los efectos cognitivos causados por el consumo de cocaina y crack, especialmente los deficits de las funciones ejecutivas, aumentan la probabilidad de un comportamiento de busqueda de drogas e interfieren en la capacidad de los usuarios de asimilar y participar en los programas de rehabilitacion. Objetivo. Determinar en la abstinencia temprana el estado de las funciones ejecutivas, la impulsividad y la ansiedad (craving) en consumidores de cocaina y crack. Sujetos y metodos. Este estudio transversal tuvo una muestra de 60 hombres, con una edad media de 31,38 ± 7,26 años, distribuidos en tres grupos: usuarios que inhalan cocaina (CDP-I; n = 15), con una edad de inicio de consumo de 23,13 ± 7,2 años; consumidores de cocaina en crack (CDP-C; n = 26), con una edad de inicio de consumo de 20,81 ± 4,21 años, y un grupo control de sujetos sin adiccion (n = 19). Se aplicaron evaluaciones sociodemograficas, clinicas y cognitivas. Resultados. Los datos mostraron diferencias significativas en las puntuaciones del nivel socioeconomico e impulsividad. Los grupos de consumidores tienen puntuaciones mas bajas con respecto al grupo control. El grupo CDP-C mostro rendimientos pobres en comparacion con el grupo CDP-I y el grupo control en las pruebas de Berg, torre de Londres, numeros en orden y sustraccion directos. El grupo CDP-I mostro una menor puntuacion en la planificacion comparada con los otros dos grupos. Conclusiones. En la abstinencia temprana, los consumidores de crack manifiestan mayor numero de deficits, principalmente en la memoria de trabajo, la planificacion y la flexibilidad cognitiva.

Similar clinical improvement and maintenance after rTMS at 5 Hz using a simple vs. complex protocol in Alzheimer's disease.

BRACKGROUND: Current treatments for Alzheimer's disease (AD) have a limited clinical response and methods, such as repetitive transcranial magnetic stimulation (rTMS), are being studied as possible treatments for the clinical symptoms with positive results. However, there is still seldom information on the type of rTMS protocols that deliver the best clinical improvement in AD. Objetive: To compare the clinical response between a simple stimulation protocol on the left dorsolateral prefrontal cortex (lDLPFC) against a complex protocol using six regions of interest. METHODS: 19 participants were randomized to receive any of the protocols. The analysis of repeated measures evaluated the change. RESULTS: Both protocols were equally proficient at improving cognitive function, behavior and functionality after 3 weeks of treatment, and the effects were maintained for 4 weeks more without treatment. CONCLUSION: We suggest rTMS on the lDLPFC could be enough to provide a clinical response, and the underlying mechanisms should be studied.

The effect of crack cocaine addiction and age on the microstructure and morphology of the human striatum and thalamus using shape analysis and fast diffusion kurtosis imaging.

The striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction (CA), showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive magnetic resonance imaging (MRI) have shown inconsistencies in volume changes, and have also shown an age effect. In this exploratory study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack CA compared to matched healthy controls (HCs), while investigating the effect of age and years of cocaine consumption. We did not find significant differences in volume and mean kurtosis (MKT) between groups. However, we found significant contraction of nucleus accumbens in CA compared to HCs. We also found significant age-related changes in volume and MKT of CA in striatum and thalamus that are different to those seen in normal aging. Interestingly, we found different effects and contributions of age and years of consumption in volume, displacement and MKT changes, suggesting that each measure provides different but complementing information about morphological brain changes, and that not all changes are related to the toxicity or the addiction to the drug. Our findings suggest that the use of finer methods and sequences provides complementing information about morphological and microstructural changes in CA, and that brain alterations in CA are related cocaine use and age differently.

Environmental enrichment prevents anxiety-like behavior induced by progesterone withdrawal in two strains of rats.

Stress vulnerability could influence the treatment response to anxiety associated with abrupt hormonal suppression. The present study explored the effects of different treatments on experimental anxiety induced by progesterone withdrawal (PW) in a stress-sensitive rat strain, Wistar Kyoto (WKY), in the burying behavior test (BBT). The following experimental series was conducted using independent groups of Wistar (control strain) and WKY ovariectomized rats: Experiment 1: Rats were treated for 5days with oil, a constant dose of progesterone (0.5mg/rat, s.c) or a combination of progesterone (0.5mg/rat, s.c) plus fluoxetine (10 mg/kg, i.p); on day 6, all rats were subjected to BBT. Experiment 2: Rats received corn oil or decreasing doses of progesterone (0.84, 0.67, 0.5, 0.33 and 0.17mg/rat; one dose daily); on day 6, the rats were subjected to BBT. Experiment 3: Rats were divided into two groups that were subjected to 30days of standard conditions or environmental enrichment (EE); from days 25 to 30, all rats received a fixed dose of progesterone (0.5mg/rat, s.c.) or vehicle. On day 31, the rats were tested with BBT. Results showed that PW increased anxiety in both strains, and fluoxetine prevented anxiety in WKY rats. In contrast, a gradual reduction of progesterone prevents the anxiety in Wistar but not in WKY. EE was preventive against the anxiety induced by PW in both strains of rats. Thus, the results suggest that anxiety induced by PW is prevented by EE while the anxiolytic effect of pharmacological treatments depends on stress vulnerability.